Myotonic muscular dystrophy (MyD) is the most prevalent human muscular dystrophy affecting several hundred thousand individuals in the United States. It is inherited as an autosomal dominant trait and is characterized by variable expressivity and late age-of-onset (birth to 70 years). The delineation of a restriction fragment length polymorphism (RFLP) that is closely linked (0 less than or equal to 0.01) to the locus for MyD would have immediate medical application for heterozygote diagnosis before the age of onset of symptoms and signs, as well as family planning and prenatal diagnosis. We propose to screen a chromosome 19 library using two experimental strategies: random screening and chromosome walking from a known linked polymorphism. We will use the linkage data available from several polymorphisms (Complement component 3, ABH secretor, Lewis, Lutheran, proline dipeptidase) in large multigenerational, tested MyD families to test the linkage of RFLPs as well as to determine the direction of chromosome walk. The walk has been initiated from a 1.4 kb unique sequence of complement component 3, which is linked to MyD, and a haplotype or "HLA-like" set of polymorphisms will be delineated as the reiterated walking procedure is continued. When a closely linked RFLP is determined (either from walking or by random screening of the chromosome 19 library), a useful probe for heterozygote diagnosis will be then available for clinical application and testing in a large population of MyD families. Methods of RNA selection and gene product analysis can then be instituted to examine the closely linked area of the chromosome to identify the mutation(s) responsible for MyD and to develop rational therapy. These experiments will also be useful in contributing linkage map information about chromosome 19, a relatively unstudied part of the human genome.